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Articles |
vβ5 and CD36, and Cross-present Antigens to Cytotoxic T Lymphocytes



Division of Hematology-Oncology, Cornell University Medical College, New York 10021
Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8+ T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the
vβ5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the
vβ5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the
vβ5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.
Key Words: dendritic cells phagocytosis CD36 integrins cross-presentation
Abbreviations used: Ann V, Annexin V; DC, dendritic cell; MCM, monocyte-conditioned medium; PI, propidium iodide; PS, phosphatidylserine.
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